The main objective of the research project is to elucidate the molecular mechanism of disorders in the ionic channels of myotonic muscles. We apply the most direct and powerful electrophysiological techniques, the voltage clamp analyses, to examine the nature of ionic channels in muscles of experimental myotonia. We are assessing the overall conductances of the sodium, potassium and chloride channels by their current-voltage relation. The functional status of each type of channel is being studied by the kinetic analyses of the voltage-dependent activation and inactivation parameters. The influence of temperature on channel conductances are also examined to determine the exact nature of the well known inverse temperature dependence of myotonia. The results of the temperature effect may be used to differentiate the abnormal ionic channels from the normal ones. The quantitative measurement of the heat of activation may help us to interpret the nature of lipid-protein interaction between the ionic channels and membrane lipids. We are also studying the actions of several antimyotonic drugs to gain some insight into the nature of the ionic channels. The data obtained in this project will be integrated to help identify the fundamental mechanism underlying the disorders of human myotonia.